Alzheimer's disease is a progressive mental deterioration in a human resulting in loss of memory, confusion and disorientation, as well as, behavioral problems such as anxiety. Alzheimer's disease accounts for the majority of senile dementias and is a leading cause of death in adults. Currently-used treatments offer a small symptomatic benefit; no treatments to delay or halt the progression of the disease are as yet available.
The cause and progression of Alzheimer's disease are not well understood. Research indicates that the disease is associated with plaques and tangles in the brain. Histologically, the brain of persons afflicted with Alzheimer's disease is characterized by a distortion of the intracellular neurofibrils and the presence of senile plaques composed of granular or filamentous argentophilic masses with an amyloid protein core, largely due to the accumulation of β-amyloid protein (Aβ) in the brain. Aβ accumulation plays a role in the pathogenesis and progression of the disease and is a proteolytic fragment of amyloid precursor protein (APP). APP is cleaved initially by β-secretase (also referred to as BACE 1 or memapsin 2) followed by γ-secretase to generate Aβ. Without being bound by theory, it is believed that one approach to the treatment of Alzheimer's disease is to inhibit the production of Aβ.
It has been discovered herein that certain quinazoline compounds, such as the dihydroquinalozines described herein, and pharmaceutically acceptable salts of the foregoing may be used for treating Alzheimer's disease. In one illustrative embodiment of the invention, compounds and pharmaceutical compositions containing the compounds are described herein for treating patients in need of relief from Alzheimer's disease. In another embodiment, methods for treating Alzheimer's disease using the compounds and compositions are described herein. In another embodiment, uses of the compounds and compositions in the manufacture of medicaments for treating Alzheimer's disease are described herein. In one aspect, the compositions, methods, and medicaments include a therapeutically effective amount of one or more of the compounds described herein.
It is appreciated that the compounds described herein may be used alone or in combination with other compounds useful for treating such diseases, including those compounds that may operate by the same or different modes of action. It is appreciated that the compounds described herein may be used in combination with compounds to improve cognitive properties as well as anxiolytics and antipsychotics to control behavior.